Inhalational anaesthetic
Inhalation anesthetics (including inhalation anesthetics ) are drugs that are used in anesthesia to maintain and further also to induction of anesthesia and be absorbed by inhalation. Inhalation anesthetics are used as gases or vaporized liquids by means of a vaporizer via a breathing mask, a laryngeal mask airway or an endotracheal tube administered. The aim of the application of anesthetic agents is the temporary elimination of consciousness and reflexes as well as the inhibition of pain.
- 3.1 blood solubility
- 3.2 liposolubility
Groups of substances
As inhalational anesthetic agents as well as the gases N2O (laughing gas, nitrous oxide ) and used ( in small scale ) xenon. Previously used substances such as chloroform and diethyl ether have today because of their toxicity and explosion hazard no longer relevant.
Gases
Nitrous oxide affects mainly analgesic ( pain relieving ), but less bewusstseinsausschaltend ( hypnotic ). It is the oldest anesthetic. In order to achieve an effective concentration of 70%, it must be added together with pure oxygen. In modern anesthesia, the effect of the nitrous oxide is optimized by the addition of other anesthetic agents. It is advantageous that the gas in the anesthesia rapidly and abflutet. Problem, the diffusion of nitrous oxide in air-filled body cavities. The medical use of nitrous oxide as an anesthetic has declined drastically in recent years.
Xenon is a modern alternative which is, however, not widely used, particularly for economic reasons.
Volatile anesthetics
Volatile anesthetics are anesthetics that have a vaporizer ( vaporizer ) of the anesthesia machine to be administered. Historically, diethyl ether and chloroform as the first volatile anesthetics of importance. Today, in the western world mainly Flurane as isoflurane, sevoflurane and desflurane are used. The bromine-containing halothane is no longer used in Europe and the U.S. in general.
Flurane characterized by Niedermolekularität, high vapor pressure, low boiling point. As functional group, they contain an ether bridge. Flurane are polyhalogenated. Therefore they are also called " Haloether ". They have very good hypnotic and small pronounced analgesic, as well as varying degrees low muscle relaxant properties. From a mono anesthesia for painful procedures is therefore not recommended in humans; the Flurane are then treated with analgesics to combine (so-called balanced anesthesia). All volatile anesthetics cause a dose-dependent loss of consciousness, respiratory depression and acceptance and / or cessation of reflex activity. Flurane are colorless and non-flammable. Its smell is pungent and irritating to the upper respiratory tract, only sevoflurane has a mild, pleasant odor and is therefore suitable as the only volatile anesthetic also for induction of anesthesia with a mask. They are inert and relatively stable to light. You do not interact with metals or plastics, but can partially solve plastics or their additives.
The Fluranen include enflurane, isoflurane, sevoflurane and desflurane, and methoxyflurane. They are commercially available as liquids. The biggest suppliers of Fluranen are Abbott Laboratories and Baxter Healthcare. In order to enable easy identification, Fluran containers are provided with a color code: orange enflurane, isoflurane, violet, yellow sevoflurane and desflurane blue.
Mechanism of Action
Inhalation anesthetics probably affect many targets. The accounting policies used in anesthesia anesthetic agents are characterized by a high lipophilicity. In addition, the chemically inert noble gas xenon is an anesthetic efficacy. Therefore, the effect of inhalation anesthetics in particular with their lipophilicity and a non-specific interaction with components of the cell membrane declared ( cf. Meyer- Overton hypothesis).
In addition to this membrane modulation are also interact with the hydrophobic parts of ion channels that are responsible for the transmission of impulses. Specific interactions with cell membrane components, such as receptor (GABA -A receptor, 5 -HT3 receptor, NMDA receptor, Mach- receptor) will be discussed as well.
Pharmacokinetics
Inhalation anesthetics are different in their physicochemical properties such as vapor pressure, the oil - gas partition coefficient and blood - gas partition coefficient. The vapor pressure and the blood - gas partition coefficient determine the uptake by the lungs, while the oil - gas partition coefficient allows a prediction of anesthetic potency. As a measure of the effectiveness of an inhalation anesthetic, the minimum alveolar concentration (MAC) is used.
Thus, the following apply MAC50 - values:
- Halothane 0.8 %;
- Isoflurane 1.2%;
- Sevoflurane 1.7%;
- Enflurane 1.7%;
- Desflurane 6.0%;
- 105% nitrous oxide.
- Xenon 71 %
Blood solubility
Inhalation anesthetics have the great advantage of the exact controllability, as they can quickly onset and offset. They are the inspiratory gas mixture ( oxygen / compressed air or oxygen / nitrous oxide ) is added to and inhaled by the patient. From the alveoli of the lungs, they pass over into the blood. The speed with which takes place this transfer depends firstly on the inspiratory concentration ( the higher the concentration in the alveolar air, the higher the concentration gradient between the air and blood, and therefore the faster the transfer into the blood ), on the other hand the solubility of the anesthetic in the blood (the better soluble, the slower the increase of the partial pressure in the blood, see also Henry's law ). The ratio of the concentration of the anesthetic in the blood to the concentration in the alveolar air is referred to as the blood / gas coefficient. A coefficient of 1 indicates that blood and air having a similar concentration in balancing the partial pressures between the two compartments in both compartments. The higher this coefficient, the better the solubility of the anesthetic is in the blood, that is the more anesthetic must be passed into the blood until it is to compensate for the partial pressure. The result is a slow uptake of the anesthetic, which is a slower falling asleep (or depth of the anesthesia). If the coefficient is, however, significantly lower than 1, this indicates a poor solubility. The partial pressure increases rapidly, which is accompanied referred to as " fast uptake " of anesthesia with fast asleep or depth of anesthesia. Similarly, a poorly soluble gas ( with low blood / gas partition coefficient ) ebbing quickly once the socket is flushed with anästhetikafreiem air mixture ( in the Narkoseausleitung ). Desflurane has the lowest blood / gas coefficients of all currently used volatile anesthetics and therefore flooded the fastest on and off. In Ausleitungszeit however the duration of the previous anesthesia plays a role, since with increasing exposure time accumulation in the body, mainly in the adipose tissue, takes place.
Fat solubility
With the blood of the volatile anesthetic spread in the body of the patient and is thereby delivered to different tissues, since here too there is a concentration gradient. Of interest to the effect of the anesthetic is the accumulation in lipophilic, so adipose tissue. The primary site of action, the central nervous system / brain, is largely composed of fat-containing structures. Therefore, due to a good lipid solubility of a volatile anesthetic rapid accumulation in the brain and thus a rapid onset of action. As a measure of the lipid solubility of the oil / gas coefficient is used (similar to the distribution coefficient). A volatile anesthetic is all the more potent, the higher the oil / gas coefficient.
Side effects
Side effects of Inhalationsanästhetia are different substance specific. A serious side effect of all inhalational anesthetics (except nitrous oxide and xenon ) is the malignant hyperthermia. In particular, since Flurane favor postoperative nausea and vomiting and lead to an increase in intracranial pressure, in previously known postoperative nausea and vomiting or prone to motion sickness and in patients with increased intracranial pressure is preferably the implementation of a total intravenous anesthesia.